The overall, long-term objective of this research program is to use genetic, immunological, and molecular approaches to define the functions that the various type 12 adenovirus (Ad12) E1A and E1B proteins play in transforming rat and mouse cells in vitro, and to understand the basis for the strong oncogenicity of this serotype and the very striking difference in viral oncogenicity between this serotype and non-oncogenic serotypes such as 2 and 5. We are also interested in determining the roles of these E1 gene products in regulating the progress of infection in permissive human cells. Our specific aims over the next five years are to: 1) Analyze the roles of the Ad12 E1b 54Kd protein in the early phase of productive infection in human cells, and in ocogenic transformation of rodent cells. 2) Extend phenotypic analysis of the Ad12 E1B 19Kd mutants with a view to determining the basis for their differential DNA degradation and transformation phenotypes and defining the role of this protein in productive infection and transformation. 3) Extend mutational analysis of the roles of Ad12 E1A gene product functions in productive infection of human cells and oncogenic transformation of rodent cells. 4) Prepare and characterize monoclonal antibodies specific for each of the various Ad12 E1A and E1B proteins.